Collective migration exhibits greater sensitivity but slower dynamics of alignment to applied electric fields.

Collective migration exhibits greater sensitivity but slower dynamics of alignment to applied electric fields.
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DOI:
10.1007/s12195-015-0383-x
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发表时间:
2015-06-01
影响因子:
2.8
通讯作者:
Asthagiri AR
Asthagiri AR
中科院分区:
工程技术4区
文献类型:
--
作者:
Lalli ML;Asthagiri AR

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在发育和疾病期间,细胞集体迁移以响应物理、化学和电线索的梯度。尽管它的生理意义和潜在的治疗应用,趋电集体细胞运动是相对不太好理解。在这里,我们分析了细胞间相互作用和电场对非转化乳腺上皮细胞MCF-10A定向迁移的联合作用。我们的数据表明,集群的细胞表现出更大的敏感性,施加电场,但更慢地比孤立的细胞对齐。聚集的细胞在比分离的细胞所需的电场弱50%的电场下实现半最大定向性;然而,聚集的细胞需要102 -4倍的时间来排列。更高的灵敏度和更慢的动力学之间的这种权衡与集体运动的更慢速度和内在方向性相关,即使在没有电场的情况下。而孤立的细胞表现出持久的随机行走,群集细胞的轨迹更弹道证明了他们的均方位移对时间的超线性依赖。因此,本质导向的、较慢聚集的细胞需要更长的时间来重定向并与电场对齐。这些发现有助于定义在生物医学应用中使用电场影响细胞运动的操作空间和工程权衡。
During development and disease, cells migrate collectively in response to gradients in physical, chemical and electrical cues. Despite its physiological significance and potential therapeutic applications, electrotactic collective cell movement is relatively less well understood. Here, we analyze the combined effect of intercellular interactions and electric fields on the directional migration of non-transformed mammary epithelial cells, MCF-10A. Our data show that clustered cells exhibit greater sensitivity to applied electric fields but align more slowly than isolated cells. Clustered cells achieve half-maximal directedness with an electric field that is 50% weaker than that required by isolated cells; however, clustered cells take ∼2-4 fold longer to align. This trade-off in greater sensitivity and slower dynamics correlates with the slower speed and intrinsic directedness of collective movement even in the absence of an electric field. Whereas isolated cells exhibit a persistent random walk, the trajectories of clustered cells are more ballistic as evidenced by the superlinear dependence of their mean square displacement on time. Thus, intrinsically-directed, slower clustered cells take longer to redirect and align with an electric field. These findings help to define the operating space and the engineering trade-offs for using electric fields to affect cell movement in biomedical applications.